KBTBD6

protein-coding

kelch repeat and BTB domain containing 6, the group of BTB domain containing

Gene summary

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Involved in proteasome-mediated ubiquitin-dependent protein catabolic process; protein K48-linked ubiquitination; and regulation of Rac protein signal transduction. Located in cytoplasm and nucleus. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_152903.5

Inheritance

—

ClinVar variants

U:53B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr13:41,127,569-41,132,802

External References & Databases

Ensembl (ENSG00000165572)

Transcript & Mutation Effects

hg38 • Region Span ~5.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KBTBD6 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 61

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152903.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			53 clinvar	8 clinvar		61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	53	8	0	61

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152903.5	RefSeq	NP_690867.3	1	MANE Select
ENST00000379485.2	Ensembl	ENSP00000368799.1	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation

Biological Process

biological_process
post-translational protein modification

Molecular Function

molecular_function
protein binding

Cellular Component

cellular_component
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379485
Coding exons: 1
Length: 5178
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.58	239	381	0.627	0.0000219	4423
Missense (PolyPhen)		48	114.62	0.41877		1401
Synonymous	-0.0176	150	150	1.00	0.00000836	1357
Loss of Function	3.72	2	19.9	0.100	0.00000121	233

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.330
RVIS EVS: -0.42
RVIS percentile EVS: 25.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.975

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium